Cardiac and vascular disease (and, specifically, atherosclerosis) have emerged as the number one killer of modern man. It is a disease of multiple risk factors, but without a proven etiology.
Regarding the currently prevailing theory of cholesterol metabolism disarray as the most important causative factor in the genesis of cardiac and vascular disease, it is remarkable that no one has ever proposed a logical justification for the existence of increased cardiovascular risk linked to the presence of increased cholesterol. The presence of such an ontological explanation would serve to bolster the selection of cholesterol as a causative factor, rather than merely as a factor associated with increased risk of vascular disease.
It is obvious, on the other hand, why animals of many species should have inordinately high platelet counts, in excess of what might be physiologic for long mammalian lives. Even while human beings had developed the genetic capacity for long lives in prehistoric times, trauma and infection were by far the most important mechanisms of demise. Life expectancies did not pass the three decade mark in many societies until the mid 19th century and continue to remain around this figure in several undeveloped nations today. Given these factors, it is obvious that the ability to achieve rapid and effective hemostasis would far outweigh the need for reduced intravascular events in nature. It is thus logical to assume that if the coagulation cascade can be demonstrated to be a participant in the development of vascular disease—which it is known to be—then it is likely that the survival traits of rapid hemostasis have long been in conflict with the requirements of long term patency. In other words, the “coagulation thermostat” has been selected for maximum rapidity and efficacy and this is in direct conflict with what is required for optimal blood vessel patency.
It is recognized from the experience of the primary applicant of this patent, as well as multiple other cardiovascular physicians that no patient with normally functioning platelets and chronic counts significantly below normal has ever presented with cardiovascular disease, acute or chronic. In addition, it is known that patients with Glanzmann's thrombasthenia, a genetic abnormality preventing platelet activation, are also immune to this disease. It is further known that patients undergoing cardiovascular bypass (“perfusion”) and extra-corporeal membrane oxygenation for the purpose of cardiothoracic surgery experience a phenomenon known as “pump head”, heretofore of unknown etiology, but logically due to activated and microaggregated platelet clusters. Finally, it is fact that the process of hemodialysis activates platelets in a manner similar to the cardiovascular bypass machines—to the extent that most patients need to be heparinized—and that patients on hemodialysis have tremendously accelerated progression of atherosclerosis.
It is known that platelets are the most unstable of all cells in the body (Ref. 1, 2). It is also known that the presence of Angiotensin II in the circulation leads to the upregulation of NF Kappa B (Nuclear Factor Kappa B) and subsequent VCAM (Vascular Cell Adhesion Molecule 1) and PAI-1 (Plasminogen Activation Inhibitor 1) production (Ref. 3), both of which enhance the progression of atherosclerosis and even gross vascular deformities such as aneurysms. Similarly, the presence and induction of activated Protein C (APC) complexes also accelerate the progression of atherosclerosis. Controversy does exist whether genetically manipulated mice with increased PAI-1 expression showed more rapid spontaneous stepwise progression of atherosclerosis with some sources adamant in denial (Ref. 4, 5) and others equally categorical in support of a factorial correlation (Ref. 6). (Note, refer to Ref. 6 also for an excellent background bibliography on current thinking regarding genesis and progression of atherosclerosis). Endothelin is felt to be another compound with a role in the genesis of atherosclerosis. Von Willebrand factor is proposed to have a role in vascular disease development and manipulation of its levels is described by U.S. Pat. No. 7,192,914. However, regardless of the individual opinions regarding causative mechanisms, there is not a single individual working on the pathogenesis of atherosclerosis today who believes that cholesterol, whether in to or a subset, is the sole or even predominant causative factor.
It is established that endovascular (i.e.: blood component) factors are more important than inherent vascular structural or chemical factors in the genesis of both micro and macrovascular disease. Specifically, contents and composition of circulating blood is more significant in the genesis of vascular pathology of all causes, whether atherosclerotic, inflammatory or other, than any structural, functional or chemical factors inherent to the vessel itself. Treatment therefore focuses on modulating the influences of these blood components, whether known or unknown.
The single most effective intervention in the prevention and treatment of vascular disease at this time remains Acetyl salicylic acid (Aspirin). Particularly for vasoocclusive disease, remarkably low doses of aspirin with remarkably low incidences of complications (less than 1% incidence of major haemorrhage) result in major outcome (death or further MI) of approximately 60%. This is even more remarkable in the light of the fact that we now know based on individual platelet function assays that up to 50% of patients treated with aspirin are non-responders, meaning genetically resistant to its acetylating effects.
It is also known that the earliest and most severe forms of atherosclerosis in the body occur at sites of maximum turbulence, such as in the aorta at the impact of a jet from a stenotic aortic valve. This mechanism of injury can only be due to intimal susceptibility or some unrecognized platelet effect, as platelets are the component of blood activated in such turbulent jets.
It is puzzling why there would be such a paucity of clinical and basic science research proceeding on the hypothesis that platelets themselves are an essential pre-requisite and final common pathway for all vascular injury. As a for instance are supplied three references (Ref. 7, 8, 9) addressing the correlation of megakaryocyte dysfunction in diseases states (specifically, diabetes), the effect of fat ingestion on platelet function and the platelet size (as a marker of platelet activation) as a positive risk for acute myocardial events (i.e.: as a marker of acute endovascular injury), respectively. Of note, however, there has not been a single study to examine whether safe reduction of platelet counts to minimum levels permissible without undue increase of major bleeding might not reduce the incidence of various vascular pathology.
Given the above clinical and basic science, as well as the fact that aspirin's effects are almost exclusively confined to the platelet component of blood, it is believed self-evident that research should concentrate on the structure and function of platelets, as well as the manipulation of said structure and function as the key to solving the riddle of the overwhelming majority of vascular diseases. A logical simple early solution to what shall indubitably prove to be an exceedingly complex mechanism and array of malfunctions is to safely manipulate the function of said platelets, as well as to regulate the anticoagulant properties of the milieu (i.e.: blood) in which they are suspended.
There is also evidence that the initial establishment of tumors is not possible without angiogenesis. In addition, is also evidence that thrombin receptors have a role in this initial angiogenesis. Platelets have a role in modulation of thrombin receptors. Reduction of platelets to safe levels would affect thrombin receptor levels.
For anyone in doubt of the veracity of the potency of platelet effect on fibroblast growth and selected cellular activity, refer to U.S. Pat. No. 5,165,938. Platelet extracts cause visible increase in fibroblast activity that can be demonstrated through gross cell culture assays. Platelets (and compounds released by platelets) have a similar inflammatory effect on white cells and multiple other blood and vascular components.
Regarding available “natural” cures, a great deal of attention has been spent on garlic and its effects. Clinical and basic research has shown little effect for garlic on its components on either cholesterol levels or coagulation. Its use has not been demonstrated to decrease cardiovascular events, or have demonstrable impact on any other medical conditions.
Curiously, though the anticoagulant properties of garlic are also known, little work has been performed to investigate these properties. All work to date has focused on the purported “anticholesterol” and “anti-oxidant” effects of garlic.
Onions are even more ignored. Used in multiple cultures worldwide as a blood thinner and “cardiac tonic”, there has nevertheless been very little research regarding its composition and effects. Yet there is not only overwhelming evidence that the onion contains compounds that have a profound impact on the entirety of hemostasis (including platelet function and the coagulation cascade), but this evidence is obvious and easily demonstrable in standard platelet and coagulation assays.
Specifically, onion juice (that has not been exposed to heat and/or denaturing solvents) has been demonstrated to contain compounds that inhibit (GR1003636 addresses Allium Sativum, but the same compounds occur in Allium Cepum) initiation of the intrinsic pathway. This can be readily observed by simply instilling onion juice into a glass test tube without additives; the onion juice prevents adherence of fibrin to the glass surface, which is an activator.
Onion juice can be demonstrated through standard assays to inhibit platelet function (red onions, white and sweet, in decreasing order of potency) more effectively than any compounds known to date (red onions reduce platelet function in excess of 95%). Compounds within onions also inhibit coagulation, primarily through reducing activation through the extrinsic pathway. They also affect the later cascade components and have regulatory effects on the intrinsic pathway.
Ironically, onions also enhance certain aspects of the coagulation process. Specifically, onion juice increases the speed of clot formation (once initiated). The addition of onion juice to fresh blood in a standard warm water bath will result in more rapid completion of clotting (once clotting is initiated). CN1102186 notes that onion juice enhances platelet agglutination.
However, the most obvious and dramatic effect of onions is on thrombolysis. Topical application of sufficient amounts of onion juice to a site anywhere approximate to a hematoma (and at sufficiently frequent intervals, approximately every 6 hours) will result in the absorption of said hematoma even days after the formation of this hematoma. Even more remarkably, re-absorption shall occur at sites where there is NEVER reabsorption without surgical drainage, such as sub-periosteal pretibial and olecranon hematomas. Due to the absence of blood flow in these areas, an incision and drainage are always necessary to prevent the progression to fibrosis and the development of permanent tissue deformity.
Hematoma resorption does not only occur in places where it never would under spontaneous circumstances, but is also accelerated, meaning absorption occurs more rapidly (approximately 5-7 times faster than without onion juice). Hematoma resorption is also more complete, reducing the incidence of residual hemosiderin deposition. Finally, hematoma resorption will occur long after it would on a spontaneous basis, up to a week after the initial injury. There is no other thrombolytic known that works beyond approximately 12 hours after initial clot formation.
Onion juice thus fits perfectly the Chinese concept of a “cardiac and circulatory tonic”. Multiple components in onion juice work together to increase the threshold of activation both of the extrinsic and intrinsic coagulation pathways, potentiate the velocity of clotting, once initiated, reduce platelet aggregation and therefore confine the extent of clotting to conform more accurately to the site of injury and dramatically increase the extent and speed of thrombolysis. In other words, it appears on the face of the current evidence that the multiple compounds contained in cold extracted onion juice work together to not only inhibit, but to rebalance hemostasis. This indeed conforms to the concept of a tonic, meaning something that improves existing function.
In conclusion, onions are known to have profound effects on all aspects of the hemostatic process. While whole onion juice (cold-extracted) is primarily inhibitory to platelet function and coagulation (extrinsic and intrinsic), it also accelerates the speed of clot formation (i.e.: the velocity of completion of enzymatic cleavage of the various components) and also accelerates the speed and extent of thrombolysis. Overall, however, the most relevant fact remains that in spite of all these demonstrable (and dramatic) effects onions have never been noted to cause excessive bleeding.